Abstract
We previously reported that mice have at least one major gene determining atherosclerosis susceptibility, Ath-1. Susceptible alleles of Ath-1 are found in strain C57BL/6J and are associated with relatively low levels of high-density lipoprotein cholesterol (HDL-C) when these mice are fed an atherogenic diet. Resistant alleles of Ath-1 are found in strains C3H/HeJ and BALB/cJ and are associated with relatively high levels of HDL-C. Data reported earlier from the set of seven recombinant inbred (RI) strains, derived from C57BL/6By and BALB/cBy, showed that these parental strains differed at Ath-1. However, due to the limited number of RI strains, it was not possible to determine with certainty whether Ath-1 was the only major gene determining atherosclerosis susceptibility in these two strains or to determine its map position accurately. In this report, examination of F1, F2, and backcross progeny from a cross between C57BL/6J and BALB/cJ demonstrates that Ath-1 is the major gene determining atherosclerotic lesion formation and HDL-C levels in female mice. The data from male animals suggest that environmental factors or modifying genes also influence male HDL-C levels and thus partly obscure the Ath-1 phenotype. HDL-C levels in F1 progeny resemble the BALB/c parent. The data from the cross provide confirmatory evidence that Ath-1 is linked to Alp-2 on chromosome 1 with a map distance of 4.8 ± 2.3 (SE). Combining these data with a previous cross between strain C57BL/6 and strain C3H/HeJ gives a map distance between Ath-1 and Alp-2 of 4.9 ± 1.8 based on 7 crossovers found among 144 tested chromosomes.
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This work was supported by Grant HL-32087 from the Heart, Lung, and Blood Institute; Biomedical Research Support Grant RR05467 from the National Institutes of Health; Grant 1858 from the Council for Tobacco Research; Grant 86-1387 from the American Heart Association, with funds contributed in part by the Alameda, Orange, and Santa Barbara County Chapters; and Grants 84-N140, 84-N141, 85-N132A, and 85-N136A from the California Affiliate of the American Heart Association.
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Paigen, B., Mitchell, D., Holmes, P.A. et al. Genetic analysis of strains C57BL/6J and BALB/cJ for Ath-1, a gene determining atherosclerosis susceptibility in mice. Biochem Genet 25, 881–892 (1987). https://doi.org/10.1007/BF00502607
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DOI: https://doi.org/10.1007/BF00502607